tbuckley/cabot-search huggingface dataset:
Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation
Authors: Songling Zhu, Shufen Zhong, Kebin Cheng, Li-Sha Zhang, Jiu-wu Bai, Zu Cao, Su Wang, Wen Chen, Shipeng Cheng, Liyan Ma, Zhiyang Ling, Yuying Huang, Wangpeng Gu, Xiaoyu Sun, Chunyan Yi, Meng Zhao, Shuo Liang, Jin-Fu Xu, Bing Sun, Yaguang Zhang
Journal: Cellular and Molecular Immunology (2023)
Cancer equity for those impacted by mass incarceration
Authors: Megha Ramaswamy, Christopher Manz, Fiona Kouyoumdjian, Noel Vest, Lisa Puglisi, Emily Wang, Chelsea Salyer, Beverly Osei, Nick Zaller, Timothy R Rebbeck
Journal: JNCI Journal of the National Cancer Institute (2023)

Abstract The cancer disparities between people with incarceration histories compared with those who do not have those histories are vast. Opportunities for bolstering cancer equity among those impacted by mass incarceration exist in criminal legal system policy; carceral, community, and public health linkages; better cancer prevention, screening, and treatment services in carceral settings; expansion of health insurance; education of professionals; and use of carceral sites for health promotion and transition to community care. Clinicians, researchers, persons with a history of incarceration, carceral administrators, policy makers, and community advocates could play a cancer equity role in each of these areas. Raising awareness and setting a cancer equity plan of action are critical to reducing cancer disparities among those affected by mass incarceration.
The Effect of Biological Treatment on Fatigue in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Authors: Berit Mære Skjellerudsveen, Inger Marie Skoie, Ingvild Dalen, Tore Grimstad, Roald Omdal
Journal: Drugs (2023)

Fatigue is a frequent complaint in patients with inflammatory bowel disease. Biological drugs have demonstrated beneficial effects on some extraintestinal manifestations, but the effect on fatigue is not clear. This study investigated the effects of biological and small molecule drugs approved for inflammatory bowel disease on fatigue. We performed a systematic review and meta-analysis of randomized, placebo-controlled trials reporting Federal Drug Agency (FDA)-approved biological and small molecule drugs for use in ulcerative colitis and Crohn's disease in which measures of fatigue were recorded before and after treatment. Only induction studies were included. Maintenance studies were excluded. We searched Embase (Ovid), Medline (Ovid), PsycINFO (Ovid), Cinahl (EBSCOhost), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov in May 2022. Risk of bias was analyzed using the Cochrane risk-of-bias tool. Standardized mean difference was used to measure the treatment effect. A total of seven randomized controlled trials composed of 3835 patients were included in the meta-analysis. All of the studies included patients with moderately to severely active ulcerative colitis or Crohn's disease. The studies used three different generic fatigue instruments: the Functional Assessment of Chronic Illness Therapy-Fatigue and the Short Form 36 Health Survey Vitality Subscale versions 1 and 2. Overall treatment with biological or small molecule agents showed a beneficial effect compared with placebo, with a standardized mean difference of 0.25 (95% confidence interval 0.15–0.34, p < 0.001). The effect was independent of type of drug or subtype of inflammatory bowel disease. The risk of bias was considered to be low for all domains except for missing outcome data. Even though the included studies were of high methodological quality, the review is limited by the small number of studies included and that the available studies were not designed to evaluate fatigue specifically. Biological and small molecule drugs used in inflammatory bowel disease have a consistent, though small, beneficial effect on fatigue.
Alteration of Gut Microbiota in Individuals at <scp>High‐Risk</scp> for Rheumatoid Arthritis Associated With Disturbed Metabolome and the Initiation of Arthritis Through the Triggering of Mucosal Immunity Imbalance
Authors: Yubin Luo, Yanli Tong, Liang Wu, Haitao Niu, Yanhong Li, Lin Chong Su, Yuxi Wu, Aline Bozec, Mario M. Zaiss, Pingying Qing, Hua Zhao, Chunyu Tan, Qiuping Zhang, Yi Zhao, Huairong Tang, Yi Liu
Journal: Arthritis & Rheumatology (2023)

Objective In this study, we aimed to decipher the gut microbiome (GM) and serum metabolic characteristic of individuals at high risk for rheumatoid arthritis (RA) and to investigate the causative effect of GM on the mucosal immune system and its involvement in the pathogenesis of arthritis. Methods Fecal samples were collected from 38 healthy individuals and 53 high‐risk RA individuals with anti–citrullinated protein antibody (ACPA) positivity (Pre‐RA), 12 of 53 Pre‐RA individuals developed RA within 5 years of follow‐up. The differences in intestinal microbial composition between the healthy controls and Pre‐RA individuals or among Pre‐RA subgroups were identified by 16S ribosomal RNA sequencing. The serum metabolite profile and its correlation with GM were also explored. Moreover, antibiotic‐pretreated mice that received GM from the healthy control or Pre‐RA groups were then evaluated for intestinal permeability, inflammatory cytokines, and immune cell populations. Collagen‐induced arthritis (CIA) was also applied to test the effect of fecal microbiota transplantation (FMT) from Pre‐RA individuals on arthritis severity in mice. Results Stool microbial diversity was lower in Pre‐RA individuals than in healthy controls. The bacterial community structure and function significantly differed between healthy controls and Pre‐RA individuals. Although there were differences to some extent in the bacterial abundance among the Pre‐RA subgroups, no robust functional differences were observed. The metabolites in the serum of the Pre‐RA group were dramatically different from those in the healthy controls group, with KEGG pathway enrichment of amino acid and lipid metabolism. Moreover, intestinal bacteria from the Pre‐RA group increased intestinal permeability in FMT mice and zonula occludens‐1 expression in the small intestine and Caco‐2 cells. Moreover, Th17 cells in the mesenteric lymph nodes and Peyer's patches were also increased in mice receiving Pre‐RA feces compared to healthy controls. The changes in intestinal permeability and Th17‐cell activation prior to arthritis induction enhanced CIA severity in PreRA‐FMT mice compared with HC‐FMT mice. Conclusion Gut microbial dysbiosis and metabolome alterations already occur in individuals at high risk for RA. FMT from preclinical individuals triggers intestinal barrier dysfunction and changes mucosal immunity, further contributing to the development of arthritis.
Factors Associated With Protection From SARS-CoV-2 Omicron Variant Infection and Disease Among Vaccinated Health Care Workers in Israel
Authors: Mayan Gilboa, Tal Gonen, Noam Barda, Shelly Cohn, Victoria Indenbaum, Yael Weiss-Ottolenghi, Sharon Amit, Keren Asraf, Gili Joseph, Tal Levin, Yara Kanaaneh, Alex Aydenzon, Michal Canetti, Laurence Freedman, Neta Zuckerman, Ella Mendelson, Ram Doolman, Yitshak Kreiss, Gili Regev-Yochay, Yaniv Lustig
Journal: JAMA Network Open (2023)

Importance A correlation between antibody levels and risk of infection has been demonstrated for the wild-type, Alpha, and Delta SARS-COV-2 variants. High rates of breakthrough infections by the Omicron variant emphasized the need to investigate whether the humoral response elicited by mRNA vaccines is also associated with reduced risk of Omicron infection and disease. Objective To investigate whether the high antibody levels in individuals who have received at least 3 doses of an mRNA vaccine are associated with reduced risk of Omicron infection and disease. Design, Setting, and Participants This prospective cohort study used serial real time–polymerase chain reaction (RT-PCR) and serological test data from January and May 2022 to assess the association of preinfection immunoglobin G (IgG) and neutralizing antibody titers with incidence of Omicron variant infection, incidence of symptomatic disease, and infectivity. Participants included health care workers who had received 3 or 4 doses of an mRNA COVID-19 vaccine. Data were analyzed from May to August 2022. Exposures Levels of SARS-CoV-2 anti–receptor binding domain IgG and neutralizing antibodies. Main Outcomes and Measures The main outcomes were incidence of Omicron infection, incidence of symptomatic disease, and infectivity. Outcomes were measured using SARS-COV-2 PCR and antigen testing and daily online surveys regarding symptomatic disease. Results This study included 3 cohorts for 3 different analyses: 2310 participants were included in the protection from infection analysis (4689 exposure events; median [IQR] age, 50 [40-60] years; 3590 [76.6%] among female health care workers), 667 participants (median [IQR] age, 46.28 (37.44,54.8); 516 [77.4%] female) in the symptomatic disease analysis, and 532 participants (median [IQR] age, 48 [39-56] years; 403 [75.8%] female) in the infectivity analysis. Lower odds of infection were observed for each 10-fold increase in preinfection IgG (odds ratio [OR], 0.71; 95% CI, 0.56-0.90) and for each 2-fold increase in neutralizing antibody titers (OR, 0.89; 95% CI, 0.83-0.95). The odds of substantial symptomatic disease were reduced for each 10-fold increase in IgG levels (OR, 0.48; 95% CI, 0.29-0.78) and for each 2-fold increase in neutralizing antibodies levels (OR, 0.86; 95% CI, 0.76-0.96). Infectivity, assessed by mean cycle threshold value, was not significantly decreased with increasing IgG or neutralizing antibodies titers. Conclusions and Relevance In this cohort study of vaccinated health care workers, IgG and neutralizing antibody titer levels were associated with protection against infection with the Omicron variant and against symptomatic disease.
Technologies and applications of single-cell DNA methylation sequencing
Authors: Fang Liu, Yunfei Wang, Hongcang Gu, Xiaoxue Wang
Journal: Theranostics (2023)

DNA methylation is the most stable epigenetic modification.In mammals, it usually occurs at the cytosine of CpG dinucleotides.DNA methylation is essential for many physiological and pathological processes.Aberrant DNA methylation has been observed in human diseases, particularly cancer.Notably, conventional DNA methylation profiling technologies require a large amount of DNA, often from a heterogeneous cell population, and provide an average methylation level of many cells.It is often not realistic to collect sufficient numbers of cells, such as rare cells and circulating tumor cells in peripheral blood, for bulk sequencing assays.It is therefore essential to develop sequencing technologies that can accurately profile DNA methylation using small numbers of cells or even single cells.Excitingly, many single-cell DNA methylation sequencing and single-cell omics sequencing technologies have been developed, and applications of these methods have greatly expanded our understanding of the molecular mechanism of DNA methylation.Here, we summaries single-cell DNA methylation and multi-omics sequencing methods, delineate their applications in biomedical sciences, discuss technical challenges, and present our perspective on future research directions.
Challenges and opportunities to computationally deconvolve heterogeneous tissue with varying cell sizes using single-cell RNA-sequencing datasets
Authors: Sean K. Maden, Sang Ho Kwon, Louise A. Huuki-Myers, Leonardo Collado-Torres, Stephanie C. Hicks, Kristen R. Maynard
Journal: Genome biology (2023)

Abstract Deconvolution of cell mixtures in “bulk” transcriptomic samples from homogenate human tissue is important for understanding disease pathologies. However, several experimental and computational challenges impede transcriptomics-based deconvolution approaches using single-cell/nucleus RNA-seq reference atlases. Cells from the brain and blood have substantially different sizes, total mRNA, and transcriptional activities, and existing approaches may quantify total mRNA instead of cell type proportions. Further, standards are lacking for the use of cell reference atlases and integrative analyses of single-cell and spatial transcriptomics data. We discuss how to approach these key challenges with orthogonal “gold standard” datasets for evaluating deconvolution methods.
A dual-regulation inducible switch system for microRNA detection and cell type-specific gene activation
Authors: Wen-Jie Shu, Kyungwoo Lee, Zhe Ma, Xiaojie Tian, Jong Seung Kim, Fu Wang
Journal: Theranostics (2023)

Rationale: MicroRNAs (miRNAs) play key roles in multiple biological processes, many of which exhibit distinct cell type-specific expression patterns.A miRNA-inducible expression system can be adapted as a signal-on reporter for detecting miRNA activity or as a cell type-specific gene activation tool.However, due to the inhibitory properties of miRNAs on gene expression, few miRNA-inducible expression systems are available, and the available systems are only transcriptional or post-transcriptional regulatory system with obvious leaky expression.Methods: To address this limitation, a miRNA-inducible expression system that can tightly control target gene expression is desirable.Here, by taking advantage of an enhanced LacI repression system and the translational repressor L7Ae, a miRNA-inducible dual transcriptional-translational switch system was designed called the miR-ON-D system.Luciferase activity assay, western blotting, CCK-8 assay and flow cytometry analysis were performed to characterize and validate this system.Results: The results demonstrated that leakage expression was strongly suppressed in the miR-ON-D system.It was also validated that the miR-ON-D system could be used to detect exogenous and endogenous miRNAs in mammalian cells.Moreover, it was shown that the miR-ON-D system could be triggered by cell type-specific miRNAs to regulate the expression of biologically relevant proteins (e.g., p21 and Bax) to achieve cell type-specific reprogramming. Conclusion:This study established a tight miRNA-inducible expression switch system for miRNA detection and cell type-specific gene activation.
Fireflies
Authors: Donna Pucciani
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Identification of Distinct Genetic Profiles of Palindromic Rheumatism Using <scp>Whole‐Exome</scp> Sequencing
Authors: Chenxiang Zheng, Fan Wang, Yue Sun, Zhuochao Zhou, Yijun You, Dongyi He, Xiaoxia Zhu, Lindi Jiang, Cui Lu, Lijun Wu, Hongzhi Wang, Hanying Mei, Ting Zeng, Hui Zheng, Jialing Teng, Honglei Liu, Xiaobing Cheng, Yutong Su, Hui Shi, Qiongyi Hu, Xueming Jian, Aamir Fahira, Qiangzhen Yang, Ke Wang, Yanqin Wen, Zhuo Wang, Jinyan Huang, Chengde Yang, Yongyong Shi, Junna Ye
Journal: Arthritis & Rheumatology (2023)

Objective Previous studies have underlined the genetic susceptibility in the pathogenesis of palindromic rheumatism (PR), but the known PR loci only partially explain the disease's genetic background. We aimed to genetically identify PR by whole‐exome sequencing (WES). Methods This multicenter prospective study was conducted in 10 Chinese specialized rheumatology centers between September 2015 and January 2020. WES was performed in 185 patients with PR and in 272 healthy controls. PR patients were divided into PR subgroups who were negative for anti–citrullinated protein antibody (ACPA−) and positive for ACPA (ACPA+) according to ACPA titer (cutoff value 20 IU/liter). We conducted whole‐exome association analysis for the WES data. We used HLA imputation to type HLA genes. In addition, we used the polygenic risk score to measure the genetic correlations between PR and rheumatoid arthritis (RA) and the genetic correlations between ACPA− PR and ACPA+ PR. Results Among 185 patients with PR enrolled in our study, 50 patients (27.02%) were ACPA+ and 135 PR patients (72.98%) were ACPA−. We identified 8 novel loci (in the ACPA− PR group: ZNF503, RPS6KL1, HOMER3, HLA–DRA; in the ACPA+ PR group: RPS6KL1, TNPO2, WASH2P, FANK1) and 3 HLA alleles (in the ACPA− PR group: HLA–DRB1*0803 and HLA–DQB1; in the ACPA+ PR group: HLA–DPA1*0401) that were associated with PR and that surpassed genome‐wide significance ( P &lt; 5 × 10 −8 ). Furthermore, polygenic risk score analysis showed that PR and RA were not similar (R 2 &lt; 0.025), whereas ACPA+ PR and ACPA− PR showed a moderate genetic correlation (0.38 &lt; R 2 &lt; 0.8). Conclusion This study demonstrated the distinct genetic background between ACPA− and ACPA+ PR patients. Additionally, our findings strengthened that PR and RA were not genetically similar.
Drug screening in zebrafish larvae reveals inflammation-related modulators of secondary damage after spinal cord injury in mice
Authors: Ana-Maria Oprişoreanu, Fari Ryan, Claire Richmond, Yuliya Dzekhtsiarova, Neil O Carragher, Thomas Becker, Samuel David, Catherina G Becker
Journal: Theranostics (2023)

Prolonged inflammation after spinal cord injury is detrimental to recovery. To find pharmacological modulators of the inflammation response, we designed a rapid drug screening paradigm in larval zebrafish followed by testing of hit compounds in a mouse spinal cord injury model. Methods: We used reduced il-1β linked green fluorescent protein (GFP) reporter gene expression as a read-out for reduced inflammation in a screen of 1081 compounds in larval zebrafish. Hit drugs were tested in a moderate contusion model in mice for cytokine regulation, and improved tissue preservation and locomotor recovery. Results: Three compounds robustly reduced il-1β expression in zebrafish. Cimetidine, an over-the-counter H2 receptor antagonist, also reduced the number of pro-inflammatory neutrophils and rescued recovery after injury in a zebrafish mutant with prolonged inflammation. Cimetidine action on il-1β expression levels was abolished by somatic mutation of H2 receptor hrh2b, suggesting specific action. In mice, systemic treatment with Cimetidine led to significantly improved recovery of locomotor behavior as compared to controls, accompanied by decreased neuronal tissue loss and a shift towards a pro-regenerative profile of cytokine gene expression. Conclusion: Our screen revealed H2 receptor signaling as a promising target for future therapeutic interventions in spinal cord injury. This work highlights the usefulness of the zebrafish model for rapid screening of drug libraries to identify therapeutics to treat mammalian spinal cord injury.
Four-Year Visual Outcomes After Intravitreous Aflibercept for Vision-Threatening Complications of Diabetic Retinopathy—Reply
Authors: Jennifer K. Sun, Adam R. Glassman, Raj K. Maturi
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
iPSC-derived reactive astrocytes from patients with multiple sclerosis protect cocultured neurons in inflammatory conditions
Authors: Janis Kerkering, Bakhrom Muinjonov, Kamil S. Rosiewicz, Sebastian Diecke, Charlotte Biese, Juliane Schiweck, Claudia Chien, Dario Zocholl, Thomas Conrad, Friedemann Paul, Marlen Alisch, Volker Siffrin
Journal: Journal of Clinical Investigation (2023)

Multiple sclerosis (MS) is the most common chronic central nervous system inflammatory disease. Individual courses are highly variable, with complete remission in some patients and relentless progression in others. We generated induced pluripotent stem cells (iPSCs) to investigate possible mechanisms in benign MS (BMS), compared with progressive MS (PMS). We differentiated neurons and astrocytes that were then stressed with inflammatory cytokines typically associated with MS phenotypes. TNF-α/IL-17A treatment increased neurite damage in MS neurons from both clinical phenotypes. In contrast, TNF-α/IL-17A-reactive BMS astrocytes cultured with healthy control neurons exhibited less axonal damage compared with PMS astrocytes. Accordingly, single-cell transcriptomic BMS astrocyte analysis of cocultured neurons revealed upregulated neuronal resilience pathways; these astrocytes showed differential growth factor expression. Furthermore, supernatants from BMS astrocyte/neuronal cocultures rescued TNF-α/IL-17-induced neurite damage. This process was associated with a unique LIF and TGF-β1 growth factor expression, as induced by TNF-α/IL-17 and JAK-STAT activation. Our findings highlight a potential therapeutic role of modulation of astrocyte phenotypes, generating a neuroprotective milieu. Such effects could prevent permanent neuronal damage.